Martin Krzywinski / Genome Sciences Center / mkweb.bcgsc.ca Martin Krzywinski / Genome Sciences Center / mkweb.bcgsc.ca - contact me Martin Krzywinski / Genome Sciences Center / mkweb.bcgsc.ca on Twitter Martin Krzywinski / Genome Sciences Center / mkweb.bcgsc.ca - Lumondo Photography Martin Krzywinski / Genome Sciences Center / mkweb.bcgsc.ca - Hilbertonians - Creatures on the Hilbert Curve
music + dance + projected visualsNosaj Thingmarvel at perfect timing


Visualization Tour, Melbourne, October 9–20, 2014


art + science activism

Watch the video of this project, which features the participants who have a BRCA mutation and their interaction with the piece. The video also highlights the design and construction of the mural.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Science and art and personal stories of cancer survivors combine into this beautiful depiction of the complexity and individuality of the genome. (Free the Data)

Human Genome Art by Humans with Genomes

I recently took part in a deeply meaningful collaboration of science, art and personal stories of cancer survivors.

Together with Joanna Rudnick and Aaron De La Cruz, we sought to create a work of art that combines the science of cancer genomics and the individuals whose lives are affected by genetic mutations in the BRCA1 and BRCA2 genes, where genomic changes drastically increase one's chances of breast and ovarian cancer.

We wanted to make something that is scientifically accurate, artistically beautiful and emotionally engaging. The complexity of the genome, the multitudes of other genes and possible mutations and the millions of personal stories of hardship and survival were just a few of the elements we wanted to include the the piece.

My role was to provide the scientific direction behind the design and incorporate it into the aesthetic of Aaron De La Cruz, a street artist from San Francisco whose work echoes information, complexity, interaction and continuity. We all have a genome — a different genome. The ways in which our genomes are different is what gives us traits like hair and eye color, but is also what makes some of us predisposed to diseases like cancer.

The mural, which includes elements drawn by the cancer survivors, is part of the Free the Data campaign, which is advocating for an open access model of genome mutation databases so that scientists everywhere can analyze it and help women make informed choices about their breast-cancer risk.

The piece Importance of Data Sharing by Nature Methods illustrated the point:

Imagine you are a physician or researcher and seek to get more confirmation on the clinical impact of particular genetic variants. If your search of public databases comes up empty this does not necessarily mean that nothing is known about the mutations in question. Rather, the information may be locked away as a trade secret in a genetic testing company’s proprietary database.

The New York Times article DNA Project Aims to Make Public a Company’s Data on Cancer Genes captures the current state of the situation.

The mural was constructed on location at InVitae in San Francisco.

A video of the project is available.

Beautiful, meaningful and personal

This work will be, as far as I know, the first human annotation of mutations in the human genome by humans whose genomes have the mutations. That's quite a term!

I've always been mindful of the necessity of the mingling of art and science. In my work I tried to add things I felt about the science I thought to create work that combines our objective understanding of the world we live in with the subjective experience of living in it. This project, by far, has been the most keenly felt.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Adding emotion, keeping the science. (Free the Data)

the design

The mural was created in San Francisco on Saturday, July 13th, 2013. We are starting with a 11' x 6' wood canvas. These dimensions reflect the ratio of lengths of BRCA1 and BRCA2 proteins (1,863 and 3,418 amino acids, respectively)

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The canvas aspect ratio reflects the ratio of BRCA1 and BRCA2 protein lengths. The proteins are represented on the canvas as lines. (Free the Data)

The BRCA1 and BRCA2 proteins are drawn on the canvas as straight-line sections.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The genes are depicted on the canvas as their protein products. (Free the Data)

The locations of the participants mutations are positioned on the protein lines as circles. For individuals with large deletions, the circle is placed at the first affected amino acid. Because BRCA1 is location on the opposite strand (anti-sense), its start on the canvas is on the right.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
11 mutations, one for each of the cancer previvor and survivor participants, are placed on the protein lines as circles. The start of BRCA1 is on the right to reflect that this gene is on the anti-sense strand. (Free the Data)

The rest of the genome is now drawn. Aaron's style is perfect for depicting information and the endless complexity of the genome and its interacting elements. We were careful to include elements that indicate that the story told today is not complete. Millions of others have mutations in thousands of other genes, each potentially life-threatening. Just as the stories of our participants will continue to evolve, other stories are waiting to be told.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
BRCA1 and BRCA2 proteins and their mutations, together with the rest of the genome. Other lines and circles hint at other genes, other mutations, as well as the biochemical interactions in the cells and personal interactions of those affected by the mutations. (Free the Data)

Once the "reference" genome is depicted, participants with BRCA1 and BRCA2 mutations will complete the art work by individually marking the positions of their mutations on the art using personalized colors. With Aaron's help, everyone created their own color by mixing primary colors.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Participants fill in their mutation circles with their personalized color. (Free the Data)

From base pair, to genome, to person, to life. All it takes is one tiny change in the genome to change a life forever.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The mutations of 11 people in the vastness of the genome. What's your story? (Free the Data)

creation of free the data mural

The BRCA1 and BRCA2 lines were placed on the canvas by first pinning two pieces of string, marked with the positions of the mutations.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
String was used to mark the placing of lines and mutations. (Free the Data)

After drawing the protein lines, it was time to fill the canvas.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Aaron De La Cruz creating the art work. Here, he is filling the space in the canvas around the BRCA1 and BRCA2 segments with his design. The project was shot with a Red Camera—this is a sequence from its render application. (Free the Data)

Over the next 4 hours, Aaron filled in the canvas with the "rest" of the genome.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Aaron De La Cruz creating the art work. Here, he is filling the space in the canvas around the BRCA1 and BRCA2 segments with his design. The project was shot with a Red Camera—this is a sequence from its render application. (Free the Data)

Participants

Lucy, Karen, Steve, Ghecemy, Joanna, Jill, Lisa, Lynn, Ruth, Jenica, Susan

Cancer previvors and survivors who have been diagnosed with a mutation on BRCA1 or BRCA2 genes.

Joanna Rudnick (director/producer)

Joanna made her directorial debut with the Emmy-nominated In the Family, a deeply personal film about coming to terms with testing positive for the breast cancer gene BRCA1 mutation and following the storylines of other women and families facing the same hard choices. In the Family premiered at Silverdocs in 2008, was broadcast nationally on PBS P.O.V. the same year and was a finalist for the NIHCM Foundation’s Health Care Radio and Television Journalism Award.

Joanna received a master’s degree in Science and Environmental Journalism from New York University and a bachelor’s degree in English from Northwestern University. Joanna loves the opportunity to teach and mentor and served as an adjunct professor at Northwestern University’s Medill School of Journalism in the past.

She has written for several publications including Audubon Magazine, The Artful Mind, The Berkshire Record and Humanities. Before finding her way to the wonderful world of documentaries, Joanna served as an Americorps volunteer, implementing project-based environmental curricula in the San Francisco Public School System.

Joanna is one of the cancer survivors whose mutations are encoded in the art.

http://kartemquin.com/about/joanna-rudnick

Aaron De La Cruz (artist)

Aaron De La Cruz's work, though minimal and direct at first, tends to overcome barriers of separation and freely steps in and out of the realms of design, graffiti, and illustration.

The parameters he has chosen to work within actually allow him to free himself and react to the very limitations he has created. This overriding structure and the lack of deliberation while moving within creates a tension when encountering his work due to the almost computer generated grid like systems he creates by unplanned markmaking. The act and the marks themselves are very primal in nature but tend to take on distinct and sometimes higher meanings in the broad range of mediums and contexts they appear in and on.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Work by Aaron De La Cruz. (Aaron De La Cruz)

His work finds strengths in the reduction of his interests in life to minimal information. De La Cruz gains from the idea of exclusion, just because you don't literally see it doesn't mean that its not there.

http://www.aarondelacruz.com

news + thoughts

Replication—Quality over Quantity

Tue 02-09-2014

It's fitting that the column published just before Labor day weekend is all about how to best allocate labor.

Replication is used to decrease the impact of variability from parts of the experiment that contribute noise. For example, we might measure data from more than one mouse to attempt to generalize over all mice.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Replication. (read)

It's important to distinguish technical replicates, which attempt to capture the noise in our measuring apparatus, from biological replicates, which capture biological variation. The former give us no information about biological variation and cannot be used to directly make biological inferences. To do so is to commit pseudoreplication. Technical replicates are useful to reduce the noise so that we have a better chance to detect a biologically meaningful signal.

Blainey, P., Krzywinski, M. & Altman, N. (2014) Points of Significance: Replication Nature Methods 11:879-880.

Background reading

Krzywinski, M. & Altman, N. (2014) Points of Significance: Analysis of variance (ANOVA) and blocking Nature Methods 11:699-700.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Designing Comparative Experiments Nature Methods 11:597-598.

...more about the Points of Significance column

Monkeys on a Hilbert Curve—Scientific American Graphic

Tue 19-08-2014

I was commissioned by Scientific American to create an information graphic that showed how our genomes are more similar to those of the chimp and bonobo than to the gorilla.

I had about 5 x 5 inches of print space to work with. For 4 genomes? No problem. Bring out the Hilbert curve!

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Our genomes are much more similar to the chimp and bonobo than to the gorilla. And, we're practically still Denisovans. (details)

To accompany the piece, I will be posting to the Scientific American blog about the process of creating the figure. And to emphasize that the genome is not a blueprint!

As part of this project, I created some Hilbert curve art pieces. And while exploring, found thousands of Hilbertonians!

Happy Pi Approximation Day— π, roughly speaking 10,000 times

Wed 13-08-2014

Celebrate Pi Approximation Day (July 22nd) with the art of arm waving. This year I take the first 10,000 most accurate approximations (m/n, m=1..10,000) and look at their accuracy.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Accuracy of the first 10,000 m/n approximations of Pi. (details)

I turned to the spiral again after applying it to stack stacked ring plots of frequency distributions in Pi for the 2014 Pi Day.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Frequency distribution of digits of Pi in groups of 4 up to digit 4,988. (details)

Analysis of Variance (ANOVA) and Blocking—Accounting for Variability in Multi-factor Experiments

Mon 07-07-2014

Our 10th Points of Significance column! Continuing with our previous discussion about comparative experiments, we introduce ANOVA and blocking. Although this column appears to introduce two new concepts (ANOVA and blocking), you've seen both before, though under a different guise.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Analysis of variance (ANOVA) and blocking. (read)

If you know the t-test you've already applied analysis of variance (ANOVA), though you probably didn't realize it. In ANOVA we ask whether the variation within our samples is compatible with the variation between our samples (sample means). If the samples don't all have the same mean then we expect the latter to be larger. The ANOVA test statistic (F) assigns significance to the ratio of these two quantities. When we only have two-samples and apply the t-test, t2 = F.

ANOVA naturally incorporates and partitions sources of variation—the effects of variables on the system are determined based on the amount of variation they contribute to the total variation in the data. If this contribution is large, we say that the variation can be "explained" by the variable and infer an effect.

We discuss how data collection can be organized using a randomized complete block design to account for sources of uncertainty in the experiment. This process is called blocking because we are blocking the variation from a known source of uncertainty from interfering with our measurements. You've already seen blocking in the paired t-test example, in which the subject (or experimental unit) was the block.

We've worked hard to bring you 20 pages of statistics primers (though it feels more like 200!). The column is taking a month off in August, as we shrink our error bars.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Analysis of Variance (ANOVA) and Blocking Nature Methods 11:699-700.

Background reading

Krzywinski, M. & Altman, N. (2014) Points of Significance: Designing Comparative Experiments Nature Methods 11:597-598.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Comparing Samples — Part I — t-tests Nature Methods 11:215-216.

Krzywinski, M. & Altman, N. (2013) Points of Significance: Significance, P values and t-tests Nature Methods 10:1041-1042.

...more about the Points of Significance column

Designing Experiments—Coping with Biological and Experimental Variation

Thu 29-05-2014

This month, Points of Significance begins a series of articles about experimental design. We start by returning to the two-sample and paired t-tests for a discussion of biological and experimental variability.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Designing Comparative Experiments. (read)

We introduce the concept of blocking using the paired t-test as an example and show how biological and experimental variability can be related using the correlation coefficient, ρ, and how its value imapacts the relative performance of the paired and two-sample t-tests.

We also emphasize that when reporting data analyzed with the paired t-test, differences in sample means (and their associated 95% CI error bars) should be shown—not the original samples—because the correlation in the samples (and its benefits) cannot be gleaned directly from the sample data.

Krzywinski, M. & Altman, N. (2014) Points of Significance: Designing Comparative Experiments Nature Methods 11:597-598.

Background reading

Krzywinski, M. & Altman, N. (2014) Points of Significance: Comparing Samples — Part I — t-tests Nature Methods 11:215-216.

Krzywinski, M. & Altman, N. (2013) Points of Significance: Significance, P values and t-tests Nature Methods 10:1041-1042.